Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease of adulthood, determined by the loss of spinal , bulbar and cortical motor neurons, which leads to paralysis of voluntary muscles involving also respiratory muscles.
Motor neurons are the cells responsible for the contraction of voluntary muscles, involved primarily for movement, but also for vital functions, such as swallowing, phonation and respiration: their degeneration implies the progressive paralysis of the muscles innervated.
ALS presents in both familial (10% of cases) and sporadic form (90% of cases). We know today the four major genes involved (SOD1, TARDPB, FUS, C9orf72) and about 15 minor genes (ALS2, SETX, VAPB, FIG4, ERBB4, MATR3, ANG, OPTN, VCP, UBQLN2, CHMP2B, PFN1, hNRPA1 A2 / B1, TUBA4A). The mutations identified to date are responsible for about 60% of familial cases and about 12% of sporadic cases.
In ALS patients cognitive and sensory abilities remain intact in most cases. The prevalence, thanks to the increase of patient taking charge, is increasing. In fact, only in Italy there are about 5,000 people with ALS, with a prevalence rate of 6-8 patients per 100,000 inhabitants. The incidence is 1-3 cases per 100,000 inhabitants per year (source: www.aisla.it). Life expectancy after diagnosis is between 3-5 years, although its course has different manifestations in each patient that is affected.
Given the great heterogeneity of this disease, the diagnosis is still complex and there are currently no effective drug therapies able to stop or significantly slow down the progression of the disease.
To date the only drug indicated for ALS is riluzole (Riluteck, Sanofi-Aventis), that can slow the disease course of few months. However, thanks to the support of technological aids, the increased awareness of patients’ needs and the rise of specialized clinical centers the quality of life of patients is much improved over the years.
Although research is making great strides on the knowledge of the mechanisms underlying the disease, there is not any effective treatments. For this reason, researchers are focusing on several fronts:
- Genetic studies are leading to the knowledge of the disease onset mechanisms, and only in 2014 two new genes have been discovered, MATR3 TUBA4A.
- New works are bringing out the importance of innate immunity and neuroinflammation in the progression of ALS, clearing the way for possible new therapeutic pathways that target active molecules in the immune system.
- Interesting results have been obtained in the field of stem cell, exploitable both as disease model and therapy. In particular, it has been proposed the use of induced pluripotent stem cells - iPSCs (Induced Pluripotent Stem Cells) – derived from fibroblasts of ALS patients as a possible cellular model for the study of the disease.
- It has been opened the way for the use of the MRSI ((Magnetic Resonance Spectroscopic Imaging) for the diagnosis and analysis of disease progression, through non-invasive techniques.
- Clinical trials are ongoing in different parts of the world with new molecules and advanced biological therapies, and also the Italian scientific community is engaged on this front. More details on clinical trials and on molecules potentially “disease modifying” already tested or under ongoing evaluation are available in the synopsis of clinical trials on ALS present in www.clinicaltrials.gov, published on the website of scientific dissemination of AriSLA Foundation www.alscience.it.